Protein interactions in the murine cytomegalovirus capsid revealed by cryoEM.
10.1007/s13238-013-3060-7
- Author:
Wong H HUI
1
;
Qiyi TANG
;
Hongrong LIU
;
Ivo ATANASOV
;
Fenyong LIU
;
Hua ZHU
;
Z Hong ZHOU
Author Information
1. The California NanoSystems Institute (CNSI), University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA.
- Publication Type:Journal Article
- MeSH:
Amino Acid Sequence;
Capsid Proteins;
chemistry;
metabolism;
ultrastructure;
Cryoelectron Microscopy;
Models, Molecular;
Molecular Sequence Data;
Muromegalovirus;
chemistry;
ultrastructure;
Protein Binding;
Protein Multimerization;
Protein Structure, Quaternary;
Protein Structure, Tertiary
- From:
Protein & Cell
2013;4(11):833-845
- CountryChina
- Language:English
-
Abstract:
Cytomegalovirus (CMV) is distinct among members of the Herpesviridae family for having the largest dsDNA genome (230 kb). Packaging of large dsDNA genome is known to give rise to a highly pressurized viral capsid, but molecular interactions conducive to the formation of CMV capsid resistant to pressurization have not been described. Here, we report a cryo electron microscopy (cryoEM) structure of the murine cytomegalovirus (MCMV) capsid at a 9.1 Å resolution and describe the molecular interactions among the ∼3000 protein molecules in the MCMV capsid at the secondary structure level. Secondary structural elements are resolved to provide landmarks for correlating with results from sequence-based prediction and for structure-based homology modeling. The major capsid protein (MCP) upper domain (MCPud) contains α-helices and β-sheets conserved with those in MCPud of herpes simplex virus type 1 (HSV-1), with the largest differences identified as a "saddle loop" region, located at the tip of MCPud and involved in interaction with the smallest capsid protein (SCP). Interactions among the bacteriophage HK97-like floor domain of MCP, the middle domain of MCP, the hook and clamp domains of the triplex proteins (hoop and clamp domains of TRI-1 and clamp domain of TRI-2) contribute to the formation of a mature capsid. These results offer a framework for understanding how cytomegalovirus uses various secondary structural elements of its capsid proteins to build a robust capsid for packaging its large dsDNA genome inside and for attaching unique functional tegument proteins outside.
